Crosstalk of autophagy and apoptosis: Involvement of the dual role of autophagy under ER stress

• Published in: Journal of cellular physiology Vol. 232; no. 11; pp. 2977 - 2984
• Main Authors: Song, Shuling, Tan, Jin, Miao, Yuyang, Li, Mengmeng, Zhang, Qiang
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2017
• Subjects: Activation; Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Autophagy; Calcium; Caspase; Cellular stress response; Crosstalk; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Homeostasis; Humans; Injury prevention; Phagocytosis; Proteins; Regulatory mechanisms (biology); Signal Transduction; Stresses; UPR; Upstream; apoptosis; autophagy; UPR; endoplasmic reticulum stress
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.25785

Endoplasmic reticulum (ER) stress is a common cellular stress response that is triggered by a variety of conditions that disturb cellular homeostasis, and induces cell apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis induced by ER stress. There are common upstream signaling pathways between autophagy and apoptosis induced by ER stress, including PERK/ATF4, IRE1α, ATF6, and Ca2+. Autophagy can not only block the induction of apoptosis by inhibiting the activation of apoptosis‐associated caspase which could reduce cellular injury, but also help to induce apoptosis. In addition, the activation of apoptosis‐related proteins can also inhibit autophagy by degrading autophagy‐related proteins, such as Beclin‐1, Atg4D, Atg3, and Atg5. Although the interactions of different autophagy‐ and apoptosis‐related proteins, and also common upstream signaling pathways have been found, the potential regulatory mechanisms have not been clearly understood. In this review, we summarize the dual role of autophagy, and the interplay and potential regulatory mechanisms between autophagy and apoptosis under ER stress condition. The dura role of autophagy, pro‐survival, and ‐death, may be dependent on the extent of ER stress, and it implements by the regulation of apoptosis. Autophagy can not only block the induction of apoptosis by inhibiting the activation of apoptosis‐associated caspase which could reduce cellular injury, but also help to induce apoptosis. In addition, the activation of apoptosis‐related proteins can also inhibit autophagy by degrading autophagy‐related proteins, such as Beclin‐1, Atg4D, Atg3, and Atg5.